As TrialSite has reported, there are growing concerns around vaccine safety and the number of adverse events that are occurring soon after the administration of the jab. The majority of these reported adverse events (AEs) are occurring after the second jab. This begs the question: why are the mRNA vaccines following a two-shot regimen? One would assume this decision was based on compelling efficacy data accumulated from the large Phase 3 trial. TrialSite posits below that the data was presented in such a way so that a two-dose regimen was deemed necessary, regardless of risk to patient. The consequence: a mounting safety crisis that could have been avoided with one dose. The data reveals that the one-shot regimen would suffice but the way the efficacy data was represented, the two-shot regimen became the apparent necessity.
Looking at the data from Pfizer’s Phase 3 trial, it becomes apparent that they reported a 94.6% relative risk reduction (aka: Vaccine Efficacy) for their two-dose regimen but only a 52.4% relative risk reduction for their single-dose regimen.
From that data, it seems clear that the two-dose regimen confers far superior protection and makes the choice between the two regimens clear. This decision to follow a two-dose regimen versus a single dose had monumental consequences for the pace and complexity of the vaccine rollout in the United States and throughout the globe. Obviously, the supply shortage immediately doubled by requiring two doses for every person. This alone would cost countless lives by delaying protection. However, the logistics of follow-up, reserving second doses, and ensuring the same vaccine is administered for both doses, were all added complexities stacked on top of an already daunting task that stalled the vaccine campaign in its early months. Another significant consequence is that the risk of adverse reactions greatly increased due to the two-dose regimen. Obviously, administering each dose poses some risk of an adverse reaction. However, the second dose is associated with far more frequent and severe reactions compared to the first dose. This is expected because the immune system has already been materially primed and will react robustly to the recognized antigen on the second dose.
Now that we’ve seen the dramatic benefits that a single dose regimen would have provided, we’ll delve into the data to determine why the two-dose regimen was chosen, but first, let’s discuss some concepts of how immunity develops over time. The human immune system is quite complex. It’s well understood that adaptive immunity takes time to develop. It starts to develop in days and ramps up quickly in weeks. However, over longer periods of time, it continues to improve through a process called affinity maturation. The details of these concepts go beyond the scope of this article but, in short, adaptive immunity takes time to develop and continues to improve over many weeks and even months.
For this reason, in order to determine the most efficacious dosing regimen, the point in time that the Vaccine Efficacy should be measured must use the same offset from the start of the various dosing regimens being compared. For example, any positive cases that occur greater than 28 days after the first dose for both the single-dose and two-dose regimens would be counted.
How was the vaccine efficacy reported from the Pfizer trial? As noted earlier, Pfizer reported a 94.6% vaccine efficacy for two doses and 52% efficacy for a single dose. However, when delving into how the industry sponsor calculated these, numbers start to unravel. The vaccine efficacy for the two-dose regimen was computed as expected. They counted any cases in the vaccinated arm that occurred at least 7 days after the second dose. The second dose was administered 21 days after the first dose. Therefore, the immune system was allotted 28 days to develop immunity.
Deviation Calculating Efficacy After First Dose
The 52.4% vaccine efficacy of the single-dose regimen was calculated using a very different approach. Pfizer counted any cases that occurred after the day the first dose was administered up to the day the second dose was administered (day 21). Therefore, no days were allotted for immunity to develop prior to counting positive cases against the single-dose regimen. Obviously, no protection is provided immediately after the first dose is administered. In fact, their own trial data shows the real efficacy of the single-dose vs two-dose regimen very clearly in their own graph included below. The blue symbols represent cases in the placebo arm. The red symbols represent cases in the vaccinated arm. Notice how the two diverge starting at day 12. This reveals when a single dose starts to provide protection. Notice how quickly the immunity builds and additional cases flatten out after 14 days. They continue on a similar flat path even after the second dose is administered on day 21. It’s clear from this Pfizer data that the efficacy of the single dose is similar to the double dose after 14 days.
This conclusion was later confirmed in real-world data provided by Israel. Israel was a leader in vaccinating a high percentage of its population. They negotiated a deal with Pfizer to obtain large volumes of early vaccine shipments in exchange for collecting extensive efficacy and safety data. From Israel’s real-world data, they confirmed that a single dose of the Pfizer/BioNTech vaccine was highly efficacious. They observed a real-world vaccine efficacy that started at day 14 and quickly ramped up to 90-91% by day 21 where it leveled off.
This would be great news except that Pfizer must have already known this. Yet they still chose to only present the two-dose regimen as a viable path, and represent a low efficacy for a single shot. Perhaps it’s a difficult decision to make inside board rooms when billions of dollars are at stake? The one thing that is certain is that there was and still is a heavy price being paid in human lives. Now many vaccine manufacturers are calling for annual booster shots being needed, additional multi-variant shots, low-risk children needing vaccines, etc. Based on the rationale of this argument, are these recommendations really based on science and health benefits or boardroom revenue forecasts? And given the significant number of safety events, where are the health regulators (FDA), monitors (CDC), and federal research sponsors (NIH) when you need them? That’s why the taxpayer funds them via Congress.
Note that prior to publishing this piece, TrialSite reached out to the company’s head of communications for a direct interaction but they declared they were too busy for any direct, two-way communication and rather offered to possibly respond to vetted questions.